Kinetic Resolution of 5-Substituted Cyclohexenols by Palladium-Catalyzed Asymmetric Redox-Relay Heck Reaction

Article abstract of DOI:10.1055/s-0035-1562620

The kinetic resolution of 2-substituted-cyclohexenols via palladium-catalyzed asymmetric redox-relay Heck reaction was realized, providing optically active 2-substituted cyclohexenols and trans-3,5-disubstituted cyclohexan-1-ones in high yield and good en

Full text of DOI:10.1055/s-0035-1562620

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
paper
A
H. Li et al.
Paper
Synthesis
Kinetic Resolution of 5-Substituted Cyclohexenols by Palladium-
Catalyzed Asymmetric Redox-Relay Heck Reaction
Hao Lia
Ang Gaoa
Xiu-Yan Liua
Chang-Hua Ding*a
Bin Xu*b
OH
O
OH
Pd(MeCN)2Cl2 (6 mol%)
ligand (13 mol%)
ArB(OH)2
+
+
Cu(OTf)2 (6 mol%), 3 Å MS
R
R
Ar
R
O
2 (balloon), DMAc, rt
(1S,5S)
(3R,5R)
(
)-cis
R = aryl, alkyl
ligand
F3C
37–57% yield
up to 62% ee
37–49% yield
up to 89% ee
Xue-Long Hou*a,c
O
N
tBu
N
a State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. of China
dingch@sioc.ac.cn
xlhou@sioc.ac.cn
b Department of Chemistry, Innovative Drug Research Center,
Shanghai University, Shanghai, 200444, P. R. of China
xubin@shu.edu.cn
c Shanghai–Hong Kong Joint Laboratory in Chemical Synthesis,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
This paper is dedicated to Professor Dieter Enders
Received: 15.07.2016
Accepted: 22.07.2016
Published online: 09.09.2016
DOI: 10.1055/s-0035-1562620; Art ID: ss-2016-z0498-op
resolution via asymmetric Heck reaction have been report-
ed.3,4 Our group has succeeded in the application of kinetic
resolution in asymmetric catalysis6 and asymmetric Heck
reaction.7 We also realized the first example of kinetic reso-
lution through Heck reaction, affording 2-substituted 2,3-
dihydrofurans and trans-2,5-disubstituted dihydrofurans in
high yield and with good enantioselectivities.7f As part of
our effort to explore further applications of this protocol in
organic synthesis, herein, we report the kinetic resolution
of 5-substituted cyclohexenols by Pd-catalyzed enantiose-
lective redox-relay Heck reaction. This kinetic resolution
reaction delivers both optically enriched arylated products
and starting materials bearing two stereocenters in high ef-
ficiency.
Initially, cis-5-phenyl-cyclohexenol (1a) was adopted as
substrate in the reaction with phenylboronic acid (2a) us-
ing Pd(MeCN)2Cl2 and PyrOx (L1) as the catalyst in N,N-di-
methylformamide (DMF) with Cu(OTf)2 and 3 Å MS as addi-
tive at room temperature (Table 1, entry1).5f,5j The Heck re-
action product 3a was afforded in 43% yield with 84% ee,
whereas 1a was recovered in 57% yield with 38% ee. By-
product 4a was also observed, with the ratio of 3a/4a being
94:6. Encouraged by these results, the impact of the reac-
tion parameters including palladium sources, solvents, li-
gands, and reaction temperature on the efficiency of kinetic
resolution was investigated (Table 1). The screening of sol-
vents including DMF, DMSO, MeOH, MeCN, DCE, toluene
and THF revealed that dimethylacetamide (DMAc) was the
best choice (entries 2–8). When DMAc was used as solvent,
3a was isolated in 49% yield with 82% ee and 1a was recov-
ered in 48% yield with 52% ee (entry 2). Different chiral N,N-
Abstract The kinetic resolution of 2-substituted-cyclohexenols via pal-
ladium-catalyzed asymmetric redox-relay Heck reaction was realized,
providing optically active 2-substituted cyclohexenols and trans-3,5-
disubstituted cyclohexan-1-ones in high yield and good enantioselec-
tivities with an S factor up to 22.
Key words palladium, Heck reaction, kinetic resolution, cyclohexenol,
cyclohexanone
Catalytic kinetic resolution, which provides a simple
and efficient way to access both products and recovered
starting materials in optical form, is one of the most useful
protocols in asymmetric synthesis.1 Classical kinetic resolu-
tion usually does not form a new chiral center in the prod-
ucts; however, recently, some reports have appeared that
involve the creation of multiple new chiral centers in prod-
ucts by catalytic kinetic resolution.2 Clearly, the develop-
ment of this type of kinetic resolution is highly desirable.
The Heck reaction is an important C–C bond-formation
reaction that is widely used in the synthesis of natural
products, medicines, and functional materials.3 The Pd-cat-
alyzed asymmetric intermolecular Heck reaction between
cyclic olefins and aryl electrophiles, so called Mizoroki–
Heck reaction, is well developed.4 Recent developments
have also revealed that acyclic substrates are suitable in the
reaction.5 Despite these significant developments, the sub-
strate scope of the asymmetric intermolecular Heck reac-
tion remains limited; furthermore, few examples for kinetic
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
H. Li et al.
Paper
Synthesis
ligands were examined (entries 9–16). Among the pyridine
oxazoline ligands, 4-CF3 variant L2 afforded similar results
to those obtained using L1 (entry 9), whereas other ligands
L3–7 gave unsatisfactory enantioselectivity (entries 10–
14). Other N,N-ligands including L8 and L9 were also exam-
ined; however, very low ee value of recovered 1a was ac-
quired (entries 15 and 16). The effect of additives on the re-
action was also examined. Of note, removing either oxygen
or 3 Å MS had little effect on the reaction, whereas no sig-
nificant reaction was observed in the absence of Cu(OTf)2
(data not shown). These results indicated the critical role of
Cu(OTf)2 in the reaction. Surprisingly, a variety of other cu-
pric salts, such as CuO, CuCl2, Cu(OAc)2, CuBr2, CuF2, CuSO4,
Cu2(OH)2CO3 did not promote the reaction (data not
shown). Changing the ratio of Pd to ligand from 6:13 to 6:3
had a detrimental effect on the kinetic resolution (data not
shown).
On the basis of the above reaction parameters investiga-
tion, the substrate scope of the kinetic resolution of 5-sub-
stituted cyclohexenol 1 with arylboronic acid 2 was exam-
ined (Table 2). Generally, the reactions provided Heck prod-
ucts 3 with trans-stereoselectivity and recovered 1 in high
yields with good enantioselectivities. The S-factor was up
to 22. The presence of electron-donating substituents on
Table 1 Optimization of Reaction Parameters for Kinetic Resolution of cis-5-Phenyl-cyclohexenola
OH
OH
O
O
Pd(CH3CN)2Cl2 (6 mol%)
ligand (13 mol%)
Ph
PhB(OH)2
+
+
+
Cu(OTf)2 (6 mol%), 3 Å MS
Ph
Ph
Ph
Ph
Ph
O2 (balloon), solvent, rt
(
)-cis-1a
2a
(1S,5S)-1a
(3R,5R)-3a
4a
F3C
O
O
O
N
O
F3C
F3C
F3C
N
N
N
N
N
N
N
tBu
tBu
iBu
iPr
L1
L2
L3
L4
L9
Ts
N
Ph
O
N
O
N
O
O
O
N
F3C
N
N
N
N
N
Bn
N
N
Ph
tBu
tBu
Ph Bn
L5
L6
L7
L8
Entry
Solvent
Ligand
1a
3a
3a/4ad
Se
Yield (%)b
ee (%)c
Yield (%)b
ee (%)c
1
2
DMF
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L8
L9
57
48
89
55
81
90
53
40
56
49
48
65
43
47
78
80
–38
–52
–8
43
49
11
26
18
5
84
82
94:6
94:6
98:2
97:3
96:4
96:4
98:2
95:5
98:2
96:4
97:3
93:6
96:4
96:4
98:2
100:0
17
DMAc
DMSO
MeOH
MeCN
DCE
17
6
3
70
4
–13
–7
72
7
5
76
8
6
4
44
3
7
toluene
THF
9
27
40
40
41
49
26
48
47
21
18
26
2
8
–24
–49
–27
30
43
3
9
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
85
20
2
10
11
12
13
14
15
16
28
–22
–51
68
2
12
3
–57
–55
10
9
51
5
–43
67
3
–15
6
a Reaction conditions: molar ratio of 1a/2a/Pd catalyst/ligand/Cu(OTf)2 = 100:80:6:13:6.
b Isolated yield.
c Determined by chiral HPLC and GC. A minus symbol means the opposite sign of optical rotation of the product.
d Determined by GC analysis.
e Calculated by the method describe by Kagan. S = ln[(1–C/100)(1–ee/100)]/ln[(1–C/100)(1+ee/100)] (C = ee/ee+ee′, ee = enantiomeric excess of recovered sub-
strate, ee′= enantiomeric excess of product).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
H. Li et al.
Paper
Synthesis
the aryl ring of phenylboronic acid had a detrimental effect
on the enantioselectivity of Heck products 3 (entries 2–6).
In addition, the enantioselectivity of the recovered cyclo-
hexenol 1 was greatly affected by the position of the sub-
stituent on the aryl ring of phenylboronic acid (entries 2–
4). The recovered 1a was a racemate when the 2-tolylbo-
ronic acid (2b) was used (entry 2). When an electron-with-
drawing substituent was introduced at the para-position of
the phenyl ring of boronic acid 2, Heck products 6 were fur-
nished with excellent ee (entries 7 and 8).
The electron-donating and -withdrawing substituents
on the aryl group of cyclohexenol 1 had a limited effect on
the enantioselectivity of Heck products 3 and recovered cy-
clohexenol 1, as its enantioselectivity was consistently
good (Table 2, entries 10 and 11). Notably, alkyl-substituted
cyclohexenols 1, such as cis-5-methyl-cyclohexenol (1d)
and cis-5-isopropyl-cyclohexenol (1e), were also suitable
substrates to produce the corresponding products in high
yield and with good enantioselectivity (entries 12–16). The
cis-5-methyl-cyclohexenol (1d) could react with several ar-
ylboronic acid derivatives, and Heck products 3 were also
obtained with over 64% enantioselectivity with 1-naphthyl
boronic acid, 2-naphthyl boronic acid and 4-methoxyphe-
nyl boronic acid. The ee of recovered cyclohexenol 1d was
greatly affected by the nature of the arylboronic acid (en-
tries 13–15).
This kinetic resolution proceeded smoothly on a 1
mmol scale. Treatment of 1.0 mmol of 1a with 0.6 mmol of
2a under optimized conditions afforded 37% yield of 3a
with 84% ee and 45% yield of 1a with 40% ee. Finally, a se-
Table 2 Substrate Scope for the Kinetic Resolution of cis-5-Substituted Cyclohexnola
OH
OH
O
O
Pd(MeCN)2Cl2 (6 mol%)
Ar
L1 (13 mol%)
ArB(OH)2
+
0.8 equiv
+
+
Cu(OTf)2 (6 mol%), 3 Å MS
O2 (balloon), DMAc, rt
R
R
R
Ar
R
(
)-cis-1
2
(1S,5S)-1
(3R,5R)-3
4
2a: Ar = Ph
2f: Ar = p-FC6H4
1a: R = Ph
2b: Ar = o-MeC6H4
2c: Ar = m-MeC6H4
2d: Ar = p-MeC6H4
2e: Ar = p-MeOC6H4
2g: Ar = MeO2CC6H4
2h: Ar = p-CHOC6H4
2i: Ar = p-BrC6H4
2j: Ar = 1-naphthyl
2k: Ar = 2-naphthyl
1b: R = p-MeOC6H4
1c: R = p-ClC6H4
1d: R = Me
1e: R = iPr
Entry
1
2
1
3
3/4d
Se
Yield (%)b
ee (%)c
Yield (%)b
ee (%)c
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1d
1d
1d
1e
2a
2b
2c
2d
2e
2f
1a, 48
1a, 50
1a, 42
1a, 45
1a, 49
1a, 45
1a, 57
1a, 47
1a, 47
1b, 41
1c, 44
1d, 39
1d, 57
1d, 38
1d, 39
1e, 47
52
0
3a, 49
3b, 37
3c, 40
3d, 43
3e, 44
3f, 38
3g, 37
3h, 42
3i, 42
3j, 47
3k, 43
3l, 46
82
50
63
62
69
57
89
88
76
81
72
81
76
74
64
85
94:6
17
96:4
–
8
3
59
44
38
53
11
35
49
52
50
51
18
38
21
59
98:2
4
99:1
7
5
92:8
8
6
99.5:0.5
99.9:0.1
93:7
6
7
2g
2h
2i
19
22
12
16
10
16
9
8
9
99.5:0.5
97:3
10
11
12
13
14
15
16
2a
2a
2a
2j
99.7:0.3
95:5
3m, 43
3n, 45
3o, 43
3p, 43
100:0
100:0
90:10
99:1
2k
2e
2a
10
6
22
a Molar ratio of 1/2/Pd(MeCN)2Cl2/L1/Cu(OTf)2 = 100:80:6:13:6.
b Isolated yield.
c Determined by chiral HPLC analysis.
d Determined by GC analysis
e Calculated by the method describe by Kagan. S = ln[(1–C/100)(1–ee/100)]/ln[(1–C/100)(1+ee/100)] (C = ee/ee+ee′, ee = enantiomeric excess of recovered
substrate 1, ee′ = enantiomeric excess of product 3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

D
H. Li et al.
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Synthesis
lection of other boronic acids, for example, methylboronic
acid, benzylboronic acid, styrylboronic acid, and cyclohex-
ylboronic acid, were subjected to the kinetic resolution; un-
fortunately, no reaction occurred (data not shown).
The absolute configuration of Heck product 3l was de-
termined to be 3R,5R by comparing its sign of optical rota-
tion with that reported previously.8 The trans-stereochem-
istry of product 3a was also supported by its X-ray diffrac-
tion analysis (Figure 1). Accordingly, the absolute
configuration of the recovered 5-phenylcyclohexenol (1a)
was determined to be 1S,5S.
with a balloon of O2 was added, and the flask was evacuated by using
a house vacuum and refilled with O2 three times while stirring. The
resulting mixture was stirred for 30 min, then cis-5-substituted cy-
cloalcohol 1 (0.2 mmol) and corresponding boronic acid 2 (0.16
mmol, 0.8 equiv) were added by using a syringe. The resulting mix-
ture was stirred until boronic acid 2 was fully consumed (reaction
monitored by TLC) at r.t. (23–25 °C). The mixture was diluted with di-
ethyl ether (10 mL) and water (2 mL), the aqueous layer was extracted
with diethyl ether (2 × 10 mL), and the combined organic layers were
washed with water (3 × 2 mL) and brine (2 mL), and dried over sodi-
um sulfate. The organic extracts were concentrated under reduced
pressure, and the resulting residue was directly subjected to flash
chromatography on silica gel (petroleum ether–EtOAc), to provide the
recovered starting material 1 and Heck product 3.
(1S,5S)-5-Phenyl-2-cyclohexenol (1a; Table 2, Entry 1)9
Yield: 16.6 mg (42%); white solid; mp 43.0–43.7 °C; 52% ee;
[α]D26 = 1.2 (c 0.64, CHCl3); HPLC (Chiralpak IC; 4.6 mm × 250 mm;
hexane/i-PrOH, 95:5; 0.7 mL/min; 214 nm): tR = 14.83 (minor), 16.13
(major) min.
IR (film): 3302.00, 3080.45, 2916.93, 1450.05, 1034.25, 911.73,
760.25, 733.44, 699.90, 676.82 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.30 (m, 2 H), 7.26–7.20 (m, 3 H),
5.87–5.83 (m, 1 H), 5.77–5.75 (m, 1 H), 4.51–4.46 (m, 1 H), 2.96–2.88
(m, 1 H), 2.32–2.25 (m, 2 H), 2.19–2.10 (m, 1 H), 1.78–1.70 (m, 1 H),
1.59 (s, 1 H).
Figure 1 X-ray crystal structure of rac-3a
13C NMR (101 MHz, CDCl3): δ = 145.56, 131.06, 128.70, 126.76,
126.36, 68.52, 39.53, 39.25, 33.76.
In conclusion, we have realized the kinetic resolution of
cis-5-substituted cyclohexenol via palladium-catalyzed en-
antioselective redox relay Heck reaction, providing exclu-
sively trans-3,5-disubstituted cyclohexanones in high yield
and ee, and recovered cis-5-substituted cyclohexenol in
high yields and with moderate to good enantioselectivities.
The extension and application of the kinetic resolution in
organic synthesis are underway in our group.
GC-MS (EI): m/z = 174.1, 1561.1, 130.1, 151.1, 104.1, 91.1, 70.0, 51.0.
HRMS (EI): m/z [M + H]+ calcd for C12H14O: 174.1045; found:
174.1048.
(1S,5S)-5-(4-Methoxyphenyl)-2-cyclohexenol (1b; Table 2, Entry
10)9
26
Yield: 16.6 mg (41%); white solid; mp 76.9–78.0 °C; 52% ee; [α]D
=
1.3 (c 0.91, CHCl3); HPLC (Chiralpak ID-3; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 92:8; 0.7 mL/min; 214 nm): tR = 8.94 (minor), 10.36 (ma-
jor) min.
All solvents were purified and dried by using standard methods prior
to use. Commercially available reagents were used without further
purification. 1H NMR spectra were recorded with an Agilent NMR in-
strument operated at 400 MHz. Chemical shifts are reported in parts
per million (ppm) with the solvent resonance as the internal standard
(CDCl3: δ = 7.26 ppm). 13C NMR spectra were recorded with a NMR
instrument operated at 101 MHz, with complete proton decoupling.
Chemical shifts are reported in ppm from tetramethylsilane with the
solvent resonance as the internal standard (CDCl3: δ = 77.1 ppm). In-
frared spectra were recorded from thin films of pure samples. Mass
and HRMS spectra were measured in EI or ESI mode and the mass an-
alyzer of the HRMS was TOF. Thin-layer chromatography was per-
formed on pre-coated glass-back plates and visualized with UV light
at 254 nm. Flash column chromatography was performed on silica gel.
Enantiomer ratios were determined by chiral HPLC or GC analysis and
compared with authentic racemic materials.
IR (film): 3351.61, 3288.55, 2937.29, 2882.13, 2838.17, 1510.56,
1247.46, 1177.87, 1028.68, 908.49, 827.59, 808.81, 727.57 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.17–7.13 (m, 2 H), 6.88–6.85 (m, 2 H),
5.86–5.82 (m, 1 H), 5.77–5.73 (m, 1 H), 4.48–4.45 (m, 1 H), 3.78 (s,
3 H), 2.90–2.83 (m, 1 H), 2.30–2.22 (m, 2 H), 2.14–2.05 (m, 1 H), 2.05–
1.65 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 158.01, 137.78, 131.01, 128.75,
127.64, 113.80, 68.54, 55.27, 39.81, 38.38, 33.94.
GC-MS (EI): m/z = 204.3, 186.2, 147.2, 134.2, 119.2, 103.1, 91.1, 77.1,
65.0, 51.0.
HRMS (EI): m/z [M + H]+ calcd for C13H16O2: 204.1150; found:
204.1151.
(1S,5S)-5-(4-Chlorophenyl)-2-cyclohexenol (1c;Table 2, Entry 11)9
27
Yield: 18.2 mg (44%); white solid; mp 75.7–76.3 °C; 50% ee; [α]D
=
General Experimental Procedure
6.2 (c 1.35, CHCl3); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/
i-PrOH, 95:5; 0.7 mL/min; 214 nm): tR = 13.54 (minor), 14.61 (major)
min.
Under a dry argon atmosphere, to a dry, 10 mL Schlenk flask
equipped with a stir bar, Pd(MeCN)2Cl2 (3.11 mg, 0.012 mmol, 6.0
mol%), Cu(OTf)2 (4.34 mg, 0.012 mmol, 6.0 mol%), L1 (7.08 mg, 0.026
mmol, 13.0 mol%), 3Å molecular sieves (30.0 mg, 150 mg/mmol) and
dimethylacetamide (2 mL) were added. A three-way adaptor fitted
IR (film): 3271.61, 3023.78, 2921.36, 1490.31, 1302.18, 1278.04,
1032.01, 912.79, 814.79, 693.55 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

E
H. Li et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.18–7.14 (m, 2 H), 7.30–7.26 (m, 2 H),
5.85–5.82 (m, 1 H), 5.77–5.74 (m, 1 H), 4.50–4.44 (m, 1 H), 2.95–2.55
(m, 1 H), 2.30–2.23 (m, 2 H), 2.13–2.05 (m, 1 H), 1.74–1.65 (m, 1 H).
GC-MS (EI): m/z = 250.1, 232.1, 207.1, 193.1, 172.1, 146.1, 133.1,
118.1, 104.1, 91.1, 78.1, 65.0, 51.0.
HRMS (EI): m/z [M + H]+ calcd for C18H18O: 250.1358; found:
250.1361.
13C NMR (101 MHz, CDCl3): δ = 143.99, 131.95, 131.12, 128.66,
128.54, 128.40, 128.12, 68.33, 39.38, 38.67, 33.68.
(3R,5R)-3-Phenyl-5-(o-tolyl)cyclohexan-1-one (3b; Table 2, Entry
GC-MS (EI): m/z = 210.2, 208.2, 190.1, 140.1, 138.1, 125.1, 103.0, 89.1,
2)
70.0, 51.1.
28
HRMS (EI): m/z [M + H]+ calcd for C12H13OCl: 208.0655; found:
208.0652.
Yield: 19.5 mg (37%); 50% ee; colorless oil; [α]D = –10.5 (c 0.55,
CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
80:20; 0.7 mL/min; 214 nm): tR = 8.65 (major), 9.65 (minor) min.
(1S,5S)-5-Methyl-2-cyclohexenol (1d; Table 2, Entry 12)9
IR (film): 3061.08, 2950.19, 1707.26, 1491.73, 1451.58, 1231.61,
1029.35, 753.41, 699.44 cm–1
.
Yield: 8.8 mg (39%); colorless oil; 51% ee; [α]D25 = –7.3 (c 0.59, CHCl3);
Chiral GC {RESTEK Rt-βDEXcst column (30 m × 0.25 mm × 0.25 μm);
carrier gas: nitrogen; injector temperature: 300 °C; split ratio: 60;
constant column flow: 10 psi; column temperature: 50 °C (2 min),
50–150 °C (3 °C/min, 5 min), 150–180 °C (5 °C /min); FID detector
temperature: 300 °C}: tR = 29.17 (major), 29.73 (minor) min.
1H NMR (400 MHz, CDCl3): δ = 5.77–5.73 (m, 1 H), 5.67–5.65 (m, 1 H),
4.31 (s, 1 H), 2.07–2.02 (m, 2 H), 1.80–1.59 (m, 3 H), 1.18–1.10 (m,
1 H), 0.99 (d, J = 6.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.37–7.29 (m, 2 H), 7.24–7.17 (m, 5 H),
7.14–7.11 (m, 2 H), 3.47–3.39 (m, 2 H), 2.81–2.66 (m, 4 H), 2.26–2.22
(m, 2 H), 2.04 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 211.85, 143.85, 135.33, 130.70,
128.76, 128.55, 127.13, 126.53, 126.44, 126.26, 125.72, 46.74, 46.02,
39.00, 28.42, 34.48, 18.92.
GC-MS (EI): m/z = 264.1, 246.1, 207.1, 186.1, 160.1, 145.1, 118.1,
104.1, 91.0, 78.0, 65.0, 51.0.
HRMS (ESI): m/z [M + NH4]+ calcd for C19H24NO: 282.1852; found:
282.1855.
13C NMR (101 MHz, CDCl3): δ = 130.91, 128.84, 69.15, 41.47, 33.69,
28.10, 21.96.
IR (film): 3322.69, 2951.43, 2909.32, 2874.21, 1453.69, 1086.38,
1064.90, 1021.73, 734.23, 675.36 cm–1
.
(3R,5R)-3-Phenyl-5-(m-tolyl)cyclohexan-1-one (3c; Table 2, Entry
3)
GC-MS (EI): m/z = 112.1, 97.1, 70.0, 69.0, 55.0.
24
HRMS (EI): m/z [M + H]+ calcd for C7H12O: 112.0888; found: 112.0893.
Yield: 21.2 mg (40%); 63% ee; colorless oil; [α]D = 12.3 (c 0.73,
CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
80:20; 0.7 mL/min; 214 nm): tR = 8.26 (major), 9.26 (minor) min.
(1S,5S)-5-Isopropyl-2-cyclohexenol (1e; Table 2, Entry 16)9
IR (film): 3057.63, 2952.37, 2915.61, 1708.26, 1603.49, 1491.60,
26
Yield: 13.7 mg (47%); colorless oil; 59% ee; [α]D = –0.3 (c 0.50,
1449.49, 1157.24, 783.63, 733.03, 698.27 cm–1
.
CHCl3); Chiral GC {RESTEK Rt-βDEXcst column (30 m × 0.25 mm ×
0.25 μm); carrier gas: nitrogen; injector temperature: 300 °C; split ra-
tio: 60; constant column flow: 10 psi; column temperature: 50 °C (2
min), 50–150 °C (3 °C/min, 5 min), 150–180 °C (5 °C/min); FID detec-
tor temperature: 300 °C}: tR = 37.67 (major), 38.22 (minor) min.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.28 (m, 2 H), 7.24–7.17 (m, 4 H),
7.03–6.96 (m, 2 H), 3.36–3.25 (m, 2 H), 2.78–2.68 (m, 4 H), 2.36–2.29
(m, 5 H).
13C NMR (101 MHz, CDCl3): δ = 211.65, 143.87, 143.82, 138.23,
128.62, 128.51, 127.84, 127.33, 127.06, 126.55, 123.99, 46.71, 46.52,
39.35, 38.86, 38.73, 21.51.
IR (film): 3321.43, 3025.63, 2956.68, 2924.49, 2871.45, 1464.98,
1385.87, 1023.94, 905.61, 729.58, 671.28 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 5.80–5.75 (m, 1 H), 5.67–5.64 (m, 1 H),
4.33–4.27 (m, 1 H), 2.12–2.07 (m, 1 H), 2.04–1.97 (m, 1 H), 1.80–1.72
(m, 1 H), 1.60 (s, 1 H), 1.56–1.43 (m, 2 H), 1.16–1.08 (m, 1 H), 0.89
(dd, J = 4.4, 6.4 Hz, 6 H).
GC-MS (EI): m/z = 264.1, 246.1, 172.1, 147.1, 132.2, 118.1, 105.1, 91.1,
77.0, 65.0, 51.0.
HRMS (EI): m/z [M + H]+ calcd for C19H20O: 264.1514; found:
264.1515.
13C NMR (101 MHz, CDCl3): δ = 131.10, 129.04, 68.82, 39.17, 36.56,
32.22, 28.63, 19.60, 19.31.
(3R,5R)-3-Phenyl-5-(p-tolyl)cyclohexan-1-one (3d; Table 2, Entry
4)
GC-MS (EI): m/z = 139.1, 122.1, 97.0, 82.1, 69.0, 55.0.
24
HRMS (EI): m/z [M + H]+ calcd for C9H16O: 140.1201; found: 140.1199.
Yield: 22.6 mg (43%); white solid; mp 59.0–59.8 °C; 62% ee; [α]D
=
23.8 (c 0.70, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 8.53 (major), 9.85
(minor) min.
(3R,5R)-3,5-Diphenylcyclohexan-1-one (3a; Table 2, Entry 1)
28
Yield: 24.3 mg (49%); white solid; mp 64.2–65.1 °C; 82% ee; [α]D
11.7 (c 0.92, CH2Cl2).
=
IR (film): 3027.40, 2924.64, 1702.82, 1514.28, 1450.03, 1234.01,
808.51, 754.10, 696.43 cm–1
.
HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH, 80:20; 0.7
mL/min; 214 nm): tR = 8.87 (major), 10.36 (minor) min.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.28 (m, 2 H), 7.24–7.17 (m, 3 H),
7.13–7.06 (m, 4 H), 3.35–3.27 (m, 2 H), 2.77–2.67 (m, 4 H), 2.35–2.30
(m, 5 H).
13C NMR (101 MHz, CDCl3): δ = 211.51, 143.89, 140.79, 136.11,
129.26, 128.59, 127.01, 126.88, 126.52, 46.66, 46.61, 39.47, 38.81,
38.45, 20.96.
IR (film): 3028.19, 2945.45, 1692.45, 1494.74, 1233.08, 1030.01,
756.00, 696.32 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.26 (m, 4 H), 7.24–7.17 (m, 6 H),
3.36–3.30 (m, 2 H), 2.79–2.69 (m, 4 H), 2.34 (t, J = 6.0 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 211.34, 143.81, 128.61, 127.01,
GC-MS (EI): m/z = 264.1, 246.1, 207.1, 172.0, 132.1, 118.1, 105.1, 91.0,
78.0, 65.0, 51.0.
126.56, 46.58, 39.40, 38.82.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

F
H. Li et al.
Paper
Synthesis
HRMS (ESI): m/z [M + NH4]+ calcd for C19H24NO: 282.1852; found:
GC-MS (EI): m/z = 308.3, 230.2, 176.2, 145.2, 131.2, 118.2, 104.2, 91.1,
282.1854.
77.1, 59.0, 51.0.
HRMS (ESI): m/z [M + NH4]+ calcd for C20H24NO3: 326.1751; found:
326.1751.
(3R,5R)-3-(4-Methoxyphenyl)-5-phenylcyclohexan-1-one (3e; Ta-
ble 2, Entry 5)
27
Yield: 24.8 mg (44%); white solid; mp 84.0–85.0 °C; 69% ee; [α]D
=
4-[(1R,5R)-3-Oxo-5-phenylcyclohexyl]benzaldehyde (3h; Table 2,
21.6 (c 1.09, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 11.31 (major), 13.06
(minor) min.
Entry 8)
25
Yield: 23.1 mg (42%); colorless oil; 88% ee; [α]D = 23.8 (c 0.71,
CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
80:20; 0.7 mL/min; 214 nm): tR = 34.89 (minor), 43.55 (major) min.
IR (film): 2950.34, 2913.44, 2886.69, 1698.14, 1510.29, 1236.67,
1178.53, 1030.52, 815.26, 758.27, 700.29 cm–1
.
IR (film): 3028.04, 2949.14, 2738.53, 1695.76, 1604.40, 1210.13,
1H NMR (400 MHz, CDCl3): δ = 7.35–7.29 (m, 2 H), 7.23–7.17 (m, 3 H),
7.11–7.09 (m, 2 H), 6.85–6.83 (m, 2 H), 3.79 (s, 3 H), 3.34–3.27 (m,
2 H), 2.77–2.65 (m, 4 H), 2.30 (t, J = 5.6 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 211.48, 135.86, 128.59, 127.97,
127.73, 127.00, 126.53, 114.14, 113.92, 55.27, 46.76, 46.69, 39.60,
38.79, 38.10.
1168.32, 838.06, 757.28, 699.46 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 9.81 (s, 1 H), 7.84–7.80 (m, 2 H), 7.36–
7.29 (m, 4 H), 7.25–7.16 (m, 3 H), 3.44–3.29 (m, 2 H), 2.82–2.71 (m,
4 H), 2.37 (t, J = 6.0 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 210.55, 191.82, 150.88, 143.38,
134.98, 130.14, 128.72, 128.64, 127.76, 126.96, 126.76, 46.46, 46.13,
39.16, 39.11, 38.91.
GC-MS (EI): m/z = 282.0, 250.1, 232.1, 172.0, 118.1, 104.1, 91.1, 78.1,
51.0.
GC-MS (EI): m/z = 278.1, 260.0, 249.0, 200.0, 146.1, 131.0, 115.1,
104.1, 91.0, 77.0, 65.0, 51.0.
HRMS (EI): m/z [M + H]+ calcd for C19H20O2: 280.1463; found:
280.1461.
HRMS (EI): m/z [M + H]+ calcd for C19H18O2: 278.1307; found:
278.1312.
(3R,5R)-3-(4-Fluorophenyl)-5-phenylcyclohexan-1-one (3f; Table
2, Entry 6)
(3R,5R)-3-(4-Bromophenyl)-5-phenylcyclohexan-1-one (3i; Table
Yield: 20.3 mg (38%); white solid; mp 75.0–76.2 °C; 57% ee;
[α]D26 = 8.0 (c 0.71, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm;
hexane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 8.58 (minor), 7.79
(major) min.
2, Entry 9)
25
Yield: 27.5 mg (42%); white solid; mp 84.7–85.6 °C; 76% ee; [α]D
=
38.1 (c 0.55, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 9.10 (minor), 10.52
(major) min.
IR (film): 3022.15, 2914.81, 2892.48, 2850.81, 1704.21, 1507.90,
1229.97, 1160.46, 816.87, 761.19, 701.93 cm–1
.
IR (film): 2942.54, 2917.76, 1699.47, 1486.22, 1260.97, 1097.29,
1H NMR (400 MHz, CDCl3): δ = 7.33–7.29 (m, 2 H), 7.25–7.12 (m, 4 H),
7.01–6.90 (m, 2 H), 3.33–3.29 (m, 2 H), 2.96–2.70 (m, 4 H), 2.33–2.29
(m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 211.13, 143.64, 128.65, 128.50,
128.43, 126.97, 126.63, 115.49, 115.28, 46.69, 46.56, 39.54, 38.79,
38.19.
1007.08, 818.01, 796.62, 764.93, 701.31 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.40 (m, 2 H), 7.33–7.28 (m, 2 H),
7.24–7.20 (m, 1 H), 7.18–7.15 (m, 2 H), 7.06–7.03 (m, 2 H), 3.31–3.27
(m, 2 H), 2.78–2.36 (m, 4 H), 2.36–2.25 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 211.07, 143.55, 142.77, 132.40,
131.89, 128.80, 128.70, 126.97, 126.69, 120.40, 117.27, 46.55, 46.36,
39.32, 38.83, 38.42.
19F NMR (400 MHz, CDCl3): δ = –116.42.
GC-MS (EI): m/z = 268.1, 250.1, 211.1, 190.1, 164.0, 136.1, 122.1,
GC-MS (EI): m/z = 329.9, 311.9, 270.9, 249.0, 224.0, 197.9, 181.9,
104.1, 91.0, 78.0, 65.0, 51.0.
133.1, 117.1, 104.0, 91.1, 77.1, 65.0, 50.0.
HRMS (EI): m/z [M + H]+ calcd for C18H17OF: 268.1263; found:
HRMS (EI): m/z [M + H]+ calcd for C18H17OBr: 328.0463; found:
268.1267.
328.0470.
Methyl 4-[(1R,5R)-3-Oxo-5-phenylcyclohexyl]benzoate (3g; Table
(3R,5R)-3-(4-Methoxyphenyl)-5-phenylcyclohexan-1-one (3j; Ta-
2, Entry 7)
ble 2, Entry 10)
25
28
Yield: 22.8 mg (37%); white solid; mp 79.1–80.3 °C; 89% ee; [α]D
=
Yield: 26.6 mg (47%); white solid; mp 84.0–85.0 °C; 81% ee; [α]D
=
39.7 (c 0.59, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 1.0 mL/min; 214 nm): tR = 19.04 (minor), 22.93
(major) min.
24.9 (c 1.11, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 11.87 (minor), 13.90
(major) min.
IR (film): 2948.00, 2903.72, 1703.84, 1280.02, 1110.30, 758.99,
IR (film): 2950.34, 2913.44, 2886.69, 1698.14, 1510.29, 1236.67,
697.17 cm–1
.
1178.53, 1030.52, 815.26, 758.27, 700.29 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99–7.96 (m, 2 H), 7.33–7.29 (m, 2 H),
7.27–7.20 (m, 3 H), 7.18–7.16 (m, 2 H), 3.90 (s, 3 H), 3.41–3.28 (m,
2 H), 2.81–2.69 (m, 4 H), 2.35 (t, J = 6.0 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.33–7.29 (m, 2 H), 7.24–7.17 (m, 3 H),
7.11–7.08 (m, 2 H), 6.86–6.83 (m, 2 H), 3.79 (s, 3 H), 3.34–3.27 (m,
2 H), 2.77–2.67 (m, 4 H), 2.30 (t, J = 6.0 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 210.72, 166.65, 143.50, 129.94,
128.68, 128.55, 127.09, 126.96, 126.69, 52.11, 46.47, 46.22, 39.21,
38.90, 36.71.
13C NMR (101 MHz, CDCl3): δ = 211.57, 143.88, 135.63, 129.74,
128.59, 127.97, 127.00, 126.53, 113.92, 55.26, 46.76, 46.68, 39.59,
38.78, 36.10.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
H. Li et al.
Paper
Synthesis
GC-MS (EI): m/z = 280.2, 223.2, 144.2, 134.2, 121.1, 104.1, 91.1, 78.0,
HRMS (EI): m/z [M + H]+ calcd for C17H18O: 238.1358; found:
65.0, 51.0.
238.1352.
HRMS (EI): m/z [M + H]+ calcd for C19H20O2: 280.1463; found:
280.1458.
(3R,5R)-3-Methyl-5-(naphthalen-2-yl)cyclohexan-1-one (3n; Table
2, Entry 14)8
28
Yield: 21.6 mg (45%); white solid; mp 82.4–84.7 °C; 74% ee; [α]D
–9.4 (c 0.70, CH2Cl2) {reported value of (3R,5R)-3n:8 80% ee; [α]D
=
=
(3R,5R)-3-(4-Chlorophenyl)-5-phenylcyclohexan-1-one (3k; Table
2, Entry 11)
–5.4 (c 0.70, CH2Cl2)}; HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 95:5; 0.7 mL/min; 214 nm): tR = 18.73 (major), 19.61 (mi-
nor) min.
28
Yield: 24.3 mg (43%); yellow solid; mp 59.0–59.8 °C; 72% ee; [α]D
=
21.2 (c 0.75, CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hex-
ane/i-PrOH, 80:20; 0.7 mL/min; 214 nm): tR = 9.11 (major), 10.65 (mi-
nor) min.
IR (film): 3054.59, 2953.79, 2923.90, 1703.92, 1204.92, 1217.52,
950.28, 900.69, 859.73, 814.31, 741.23 cm–1
.
IR (film): 2896.67, 2871.23, 1704.32, 1491.41, 1242.67, 1090.26,
838.55, 818.52, 698.92 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.98–7.88 (m, 1 H), 7.81–7.79 (m, 3 H),
7.62 (s, 1 H), 7.54–7.43 (m, 1 H), 7.37 (dd, J = 8.8, 2.0 Hz, 1 H), 3.59–
3.52 (m, 1 H), 2.78–2.56 (m, 3 H), 2.31–2.24 (m, 1 H), 2.22–2.15 (m,
2 H), 1.97–1.91 (m,1 H), 1.05 (d, J = 6.8 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 211.59, 141.72, 128.51, 128.25,
127.73, 127.67, 127.52, 126.17, 125.71, 125.63, 125.13, 48.58, 46.98,
39.65, 39.23, 29.21, 20.38.
1H NMR (400 MHz, CDCl3): δ = 7.33–6.83 (m, 9 H), 3.33–3.28 (m, 2 H),
2.79–2.70 (m, 4 H), 2.33–2.29 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 210.94, 143.57, 142.24, 132.32,
128.72, 128.67, 128.39, 126.96, 126.66, 46.54, 46.39, 39.36, 38.80,
38.83.
MS (EI): m/z = 284, 266, 249, 227, 206, 152, 138, 133, 118, 104, 91, 77.
HRMS (EI): m/z [M + H]+ calcd for C18H17OCl: 284.0968; found:
GC-MS (EI): m/z = 238.1, 181.1, 154.1, 141.1, 128.1, 115.1, 83.0, 56.0.
HRMS (ESI): m/z [M + NH4]+ calcd for C17H22NO: 256.1696; found:
256.1698.
284.0962.
(3R,5R)-3-Methyl-5-phenylcyclohexan-1-one (3l; Table 2, Entry
(3R,5R)-3-(4-Methoxyphenyl)-5-methylcyclohexan-1-one (3o; Ta-
12)8
ble 2, Entry 15)8
27
Yield: 17.1 mg (46%); colorless oil; 81% ee; [α]D = –20.4 (c
28
Yield: 18.6 mg (43%); colorless oil; 64% ee; [α]D = –8.7 (c 0.69,
0.50,CH2Cl2) {reported value of (3R,5R)-3l:8 81% ee; [α]D = –22.3 (c
0.50, CH2Cl2)}; HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
98:2; 0.5 mL/min; 210 nm): tR = 28.25 (major), 32.17 (minor) min.
CH2Cl2) {reported value of (3R,5R)-3o:8 86% ee; [α]D = –20.0 (c 0.30,
CH2Cl2)}; HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
90:10; 0.5 mL/min; 280 nm): tR = 23.68 (major), 26.03 (minor) min.
IR (film): 2957.51, 2923.94, 1710.74, 1453.22, 1261.27, 1239.42,
IR (film): 2954.81, 2922.48, 1707.25, 1611.17, 1511.89, 1458.52,
1074.89, 1026.17, 799.82, 757.21, 701.24 cm–1
.
1246.93, 1179.68, 1033.26, 872.84, 830.64 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.32 (t, J = 6.8 Hz, 2 H), 7.24–7.20 (m,
3 H), 3.42–3.35 (m, 1 H), 2.65–2.53 (m, 3 H), 2.31–2.24 (m, 1 H), 2.18
(dd, J = 14.0, 6.4 Hz, 1 H), 2.11–2.04 (m, 1 H), 1.90–1.84 (m, 1 H), 1.04
(d, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 211.60, 144.30, 128.56, 126.91,
126.47, 48.42, 47.16, 39.51, 39.30, 29.24, 20.26.
1H NMR (400 MHz, CDCl3): δ = 7.15–7.11 (m, 2 H), 6.89–6.84 (m, 2 H),
3.79 (s, 3 H), 3.36–3.31 (m, 1 H), 2.58–2.52 (m, 3 H), 2.28–2.22 (m,
1 H), 2.18–2.13 (m, 1 H), 2.07–2.00 (m, 1 H), 1.87–1.81 (m, 1 H), 1.03
(d, J = 6.8 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 211.84, 158.09, 136.45, 127.88,
113.89, 55.26, 48.48, 47.45, 39.50, 38.77, 29.22, 20.31.
GC-MS (EI): m/z = 188.1, 173.1, 131.1, 118.1, 104.1, 91.1, 78.1, 56.1,
51.0.
HRMS (ESI): m/z [M + H]+ calcd for C13H17O: 189.1274; found:
189.1274.
GC-MS (EI): m/z = 218.1, 161.1, 146.1, 134.2, 119.1, 103.1, 91.1, 77.0,
56.1.
HRMS (EI): m/z [M + H]+ calcd for C14H18O2: 218.1307; found:
218.1302.
(3R,5R)-3-Methyl-5-(naphthalen-1-yl)cyclohexan-1-one (3m; Ta-
(3R,5R)-3-Isopropyl-5-phenylcyclohexan-1-one (3p; Table 2, Entry
16)
ble 2, Entry 13)8
28
Yield: 20.4 mg (43%); colorless oil; 76% ee; [α]D = –78.1 (c 0.44,
28
Yield: 18.4 mg (43%); colorless oil; 85% ee; [α]D = –27.7 (c 0.80,
CH2Cl2) {reported value of (3R,5R)-3m:8 87% ee; [α]D = –19.7 (c 1.00,
CH2Cl2)}; HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH,
95:5; 0.7 mL/min; 214 nm): tR = 16.91 (major), 18.28 (minor) min.
CH2Cl2); HPLC (Chiralpak IC; 4.6 mm × 250 mm; hexane/i-PrOH, 98:2;
0.5 mL/min; 210 nm): tR = 24.48 (major), 29.09 (minor) min.
IR (film): 2958.41, 2874.54, 1707.71, 1451.30, 1231.21, 759.13,
IR (film): 3048.84, 2953.19, 2924.78, 1704.80, 1273.75, 1237.58,
699.24 cm–1
.
774.16, 733.22 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.30 (m, 2 H), 7.24–7.20 (m, 3 H),
3.43–3.37 (m, 1 H), 2.71–2.58 (m, 2 H), 2.48 (dd, J = 14.8, 4.8 Hz, 1 H),
2.36–2.30 (m, 1 H), 2.06–1.98 (m, 2 H), 1.73–1.64 (m, 1 H), 1.58–1.50
(m, 1 H), 0.89 (t, J = 6.0 Hz, 6 H).
13C NMR (101 MHz, CDCl3): δ = 212.28, 144.34, 128.55, 126.98,
126.41, 46.51, 44.63, 40.11, 39.38, 35.28, 30.49, 19.96, 19.92.
1H NMR (400 MHz, CDCl3): δ = 8.07 (d, J = 8.4 Hz, 1 H), 7.89 (dd, J = 8.0,
1.6 Hz, 1 H), 7.76 (d, J = 8.4 Hz, 1 H), 7.57–7.41 (m, 3 H), 7.35–7.29 (m,
1 H), 4.33–4.22 (m, 1 H), 2.77 (d, J = 6.8 Hz, 1 H), 2.65–2.59 (m, 1 H),
2.25–2.16 (m, 3 H), 2.05–1.97 (m, 1 H), 1.07 (d, J = 6.4 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 212.22, 129.12, 127.63, 127.24,
126.14, 125.58, 125.39, 125.34, 1123.48, 122.89, 48.85, 46.71, 38.50,
34.89, 29.21, 20.56.
GC-MS (EI): m/z = 216.0, 201.1, 173.2, 159.2, 146.1, 131.1, 117.2,
104.1, 91.1, 69.1, 55.0.
GC-MS (EI): m/z = 238.1, 181.1, 153.1, 128.1, 115.1, 76.0, 56.1.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
H. Li et al.
Paper
Synthesis
HRMS (EI): m/z [M + H]+ calcd for C15H20O: 216.1514; found:
216.1518.
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Acknowledgment
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thesis 2016, 48, 1483.
We acknowledge financial support by National Natural Science Foun-
dation of China (NSFC) (21532010, 21372242, 21472214, 21421091),
the NSFC and the Research Grants Council of Hong Kong Joint Re-
search Scheme (21361162001), the Chinese Academy of Sciences, the
Technology Commission of Shanghai Municipality, and the Croucher
Foundation of Hong Kong.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562620.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H